Base-Catalyzed Cascade Cyclization of Acyl Cyanides and Isocyanates for the Synthesis of Oxazoles

Abstract

Oxazoles are key heterocyclic motifs in pharmaceuticals and natural products. We report a base-promoted method for the synthesis of oxazoles from acyl cyanides and isocyanates under mild conditions. Using KOH as a catalyst in acetonitrile at 80 °C, a variety of acyl cyanides with different substituents were cyclized efficiently, yielding oxazoles in good to excellent yields (up to 98%). A plausible mechanism involving 1,1-addition, 1,3-H shift, and intramolecular cyclization is proposed. This work offers a straightforward and versatile approach to oxazole synthesis.